Document Detail

Evaluation of subchronic toxicity of pet food contaminated with melamine and cyanuric acid in rats.
MedLine Citation:
PMID:  19801503     Owner:  NLM     Status:  MEDLINE    
Outbreaks of food-associated renal failure in pets occurred in Asia and the United States of America in 2004 and 2007. They were related to the combined intoxication of cyanuric acid and melamine. Our aims were to investigate cyanuric acid and melamine contamination of pet food and to examine subchronic toxicity in rats. Levels of 10%, 20%, 50%, and 50%-100% (w/w) of contaminated pet food were fed to rats for three months. Analytical results revealed that the tainted food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the diet of 50%-100% for three months exhibited elevated serum blood urea nitrogen and creatinine, as well as dose-dependent melamine/cyanuric acid crystal-induced nephrotoxicity. The melamine/cyanuric acid crystals of various sizes were mixed with necrotic cell debris and inflammatory cells, accompanied by tubular dilation and interstitial fibrosis. The immunohistochemistry index of proliferative cellular nuclear antigen and osteopontin in the kidney of the 50%-100% group were elevated, indicating regeneration of renal cells and the formation of crystals. In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity.
Kun-Chao Chen; Chen-Wei Liao; Fen-Pang Cheng; Chi-Chung Chou; Shih-Chien Chang; Jhaol-Huei Wu; Jyh-Myng Zen; Yng-Tay Chen; Jiunn-Wang Liao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicologic pathology     Volume:  37     ISSN:  1533-1601     ISO Abbreviation:  Toxicol Pathol     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-17     Completed Date:  2010-02-18     Revised Date:  2012-01-05    
Medline Journal Info:
Nlm Unique ID:  7905907     Medline TA:  Toxicol Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  959-68     Citation Subset:  IM    
Graduate Institute of Veterinary Pathobiology, National Chung-Hsing University, Taichung, Taiwan, ROC.
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MeSH Terms
Animal Feed / analysis*
Body Weight / drug effects
Drinking / drug effects
Eating / drug effects
Food Contamination*
Kidney / drug effects,  metabolism,  pathology
Mycotoxins / analysis,  toxicity
Osteopontin / metabolism
Proliferating Cell Nuclear Antigen / metabolism
Rats, Sprague-Dawley
Renal Insufficiency / chemically induced,  pathology,  veterinary
Toxicity Tests
Triazines / analysis,  toxicity*
Reg. No./Substance:
0/Mycotoxins; 0/Proliferating Cell Nuclear Antigen; 0/Triazines; 106441-73-0/Osteopontin; 108-78-1/melamine; 108-80-5/cyanuric acid

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